SLE is a chronic disease that rarely remits and for which there is no cure. Patients who acquire SLE in childhood or adolescence have the potential to face a lifetime of complications related to their disease and its treatment. Characterizing the long-term outcomes of these patients can provide important prognostic information and help identify strategies to improve care for all SLE patients. The present study was designed to examine several important outcomes of cSLE, and to compare long-term outcomes between subjects with cSLE and aSLE utilizing the UCSF LOS.
In the UCSF LOS, ~10% of the subjects were diagnosed with SLE in childhood. Childhood-onset SLE subjects were more likely to be nonwhite and male than aSLE subjects, which is consistent with reported differences in the epidemiology of cSLE and aSLE (25
After a mean disease duration of 16.5 years and 13.4 years, respectively, almost one-quarter of the cSLE cohort and nearly half of the aSLE cohort reported a disease flare within the 3 months prior to their second LOS interview. Additionally, 68% of the cSLE cohort and 43% of the aSLE cohort were taking oral steroids. Taken together, these findings suggest that a significant percentage of both cSLE and aSLE subjects have continued disease activity despite a long disease duration. A limited number of prior studies have examined ongoing disease activity in SLE of subjects with similar disease duration. Although different measurements of disease activity were used, the findings in this study were similar to the study by Chalom et al, in which 50% of adult cSLE patients were found to have active disease after 13 years of followup (13
). Similarly, in a multicenter European study designed to examine the disease course of aSLE patients who had had SLE for 10 years or more, Swaak et al reported that 72% of subjects were still being treated with corticosteroids and 24% with an immunosuppressive and/or cytotoxic drug after a mean disease duration of 16 years (16
Comparison of disease activity using 3 self-reported tools demonstrated reduced disease activity among cSLE versus aSLE subjects. Given the lower disease activity in the cSLE subgroup, we were surprised to find that a significantly higher proportion of cSLE subjects (68%) versus aSLE subjects (43%) were still receiving oral steroids at the time of followup. Additionally, cSLE subjects were more likely to have received IV steroids and MMF in the months prior to followup, suggesting more intensive therapy overall. The reasons for the discrepancy between disease activity and increased immunosuppressive treatment in the cSLE cohort are unclear. Because cSLE subjects are more likely to have a history of renal disease, there may be reluctance on the part of the prescribing physician to alter medication regimens for patients who have had severe organ involvement. Alternatively, this difference in disease activity and steroid use could suggest that cSLE patients continue to need more medications than aSLE patients to maintain disease remission. A final possibility we explored was that cSLE subjects, who were more likely to be recruited from UCSF-affiliated practices, would also be more likely to be prescribed steroids because of differences in prescribing patterns between study recruitment sites or the primary SLE physician. However, after excluding subjects recruited from UCSF-affiliated clinics from the analysis, the use of steroids was still significantly higher in the cSLE subgroup (61.7 versus 39.9; P = 0.003). In addition, independent of the primary SLE physician, cSLE subjects were more likely to be receiving steroids.
Analysis of differences in past medication use between the cSLE and aSLE cohorts revealed that 100% of the subjects in the cSLE cohort had previously received steroids, which is consistent with findings in other studies of cSLE in which the majority of patients require steroids for disease control (3
). It is also possible that higher rates of steroid use in the cSLE cohort maybe be due to differences in prescribing patterns between pediatric and adult rheumatologists.
Our study demonstrated that subjects with cSLE were more likely to have renal disease than subjects with aSLE, and in multivariate analysis cSLE was found to be an independent predictor of renal disease. We found that nearly 20% of the cSLE subjects required dialysis and 12% had had a renal transplant. Thus, not only are patients with cSLE more likely to develop renal disease than those with aSLE, but those that do develop renal involvement have poor outcomes. These findings are similar to previous observations regarding the outcomes of lupus nephritis in children. In a 1992 study by McCurdy et al, 22% of patients with cSLE and nephritis progressed to end-stage renal disease (27
). These findings underscore the need for aggressive management of renal disease in cSLE patients. The high number of nephrology visits among the cSLE cohort suggests that cSLE patients continue to have an ongoing need for close monitoring by a nephrologist, either as a result of active disease or chronic damage from SLE.
Cardiovascular disease is emerging as a significant cause of early morbidity and mortality in patients with cSLE (28
). In our study, 7 subjects in the cSLE cohort reported a history of at least 1 MI. These findings are consistent with previous studies noting a high rate of cardiovascular disease among young adults with SLE (29
). Additionally, in our cohort, cSLE was an independent risk factor for MI. It should be noted that this model included demographic risk factors only, and did not include other traditional and disease-related cardiovascular risk factors such as history of hypertension, smoking, disease activity, and steroid use.
In this study, we compared the long-term outcomes (average disease duration >10 years) of nearly 900 adult subjects with childhood- and adult-onset SLE utilizing self-reported outcomes. The primary strength of this study is that the LOS is a large cohort, diverse in regard to the demographics of the study population and the range of both medical and psychosocial burden of disease. In addition, the LOS includes one of the largest known cohorts of subjects with cSLE.
As with any cross-sectional, observational study, the results need to be interpreted with caution. Because this study relies on subject self-reported outcomes, inaccuracies in subject reporting may occur. This limitation was addressed in part by validating a subset of the self-reported outcomes through chart review.
At present, we are not able to assess cumulative disease damage in the LOS, although an effort is underway to address this limitation. A limited number of prior studies have demonstrated that cSLE patients have more permanent damage than aSLE patients when followed over similar time periods, and that cSLE patients are more likely to have disease damage in the renal and neuropsychiatric domains (14
). In a retrospective study by Miettenun et al, 51 patients with cSLE had a mean Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index score of 2.1 after only 7.2 years of followup, and 69% had damage in at least 1 organ or system (5
). In comparison, in a study of aSLE subjects, only 54% of the cohort had damage after 11.9 years (30
). Ongoing disease activity and high-dose steroid use have been identified as predictors of disease damage in cSLE (18
). Although damage was not directly assessed in this study, given the high rates of end-stage renal disease in the cSLE cohort, the high disease activity, and the prolonged use of steroids, it is likely that the disease-related damage would be higher in the cSLE subgroup of the LOS as well.
Despite these limitations, the study design of the LOS is ideal for examining the late outcomes of a rare chronic disorder and provides unique insight into the long-term outcomes of both cSLE and aSLE. In contrast, a prospective inception cohort study of similar size could be significantly more difficult and costly.
In conclusion, although cSLE subjects in the LOS reported lower disease activity than their adult counterparts, they were more likely to be on immunosuppressive therapies associated with active disease and had frequent encounters with medical providers. In addition, cSLE subjects had a higher frequency of renal involvement and a higher than expected risk of MI. These findings highlight the high burden of disease associated with cSLE, and the need to provide ongoing and comprehensive clinical support for these patients as they transition from pediatric to adult rheumatology care. This study demonstrates important differences in cSLE and aSLE outcomes, and underscores the potential need for identifying specific strategies for the treatment of cSLE that may differ from traditional therapeutic strategies for management of aSLE.